Photochemical Intermolecular [3σ + 2σ]-Cycloaddition for the Construction of Aminobicyclo[3.1.1]heptanes.

The development of synthetic strategies for the preparation of bioisosteric compounds is a demanding undertaking in medicinal chemistry. Numerous strategies have been developed for the synthesis of bicyclo[1.1.1]pentanes (BCPs), bridge-substituted BCPs, and bicyclo[2.1.1]hexanes. However, progress on the synthesis of bicyclo[3.1.1]heptanes, which serve as meta-substituted arene bioisosteres, has not been previously explored. Herein, we disclose the first photoinduced [3σ + 2σ] cycloaddition for the synthesis of trisubstituted bicyclo[3.1.1]heptanes using bicyclo[1.1.0]butanes and cyclopropylamines. This transformation not only uses mild and operationally simple conditions but also provides unique meta-substituted arene bioisosteres. The applicability of this method is showcased by simple derivatization reactions.

Citation

Yongxiang Zheng, Weichen Huang, Roshan K Dhungana, Albert Granados, Sebastian Keess, Mehran Makvandi, Gary A Molander. Photochemical Intermolecular [3σ + 2σ]-Cycloaddition for the Construction of Aminobicyclo[3.1.1]heptanes. Journal of the American Chemical Society. 2022 Dec 28;144(51):23685-23690

Mesh Tags

Substances

PMID: 36523116

search → result